Abnormal neurovascular control during central and peripheral chemoreceptors stimulation in heart failure patients with preserved ejection fraction

Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF.

Patients aged 55–80 years with symptoms of heart failure, body mass index ≤ 35 kg/m², left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m², left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e′ index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O₂ and 90% N₂, with CO₂ titrated) and central chemoreceptors stimulation (7% CO₂ and 93% O₂) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography.

During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF.

Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.